Reduced islet ? cell number and function underlie the progression of all forms of diabetes. It is therefore essential for all laboratories investigating causes and potential cures for diabetes to be able to study islet function in relation to their specific models and molecules of interest. The objective of the Islet Cell Biology Core (ICBC) is to provide DRC members with state of the art support including experiment design, islet isolation, and performance of and/or training in an expansive range of assays for physiological and morphometric assessment of pancreatic islet function and growth. This will be accomplished through four Aims: Aim 1: To provide islet isolation service and training: We will continue to offer islet isolation services using rodent animal models. Depending on the needs of specific investigators, the ICBC provides training for graduate students, postdoctoral fellows and research staff in pancreatic islet isolation techniques. Aim 2: To provide state of the art assays for physiological assessment of islet function: We will continue to provide consultation on experimental design and to offer a broad range of assays of pancreatic islet function, including batch incubation and perifusion, islet and cell fluorescence imaging (Cai2+), mitochondrial function assays by Seahorse Extracellular Flux Analyzer, perifusion coupled with respirometry, and closed respirometry. We will continue to provide access and instruction for quantitative imaging of pancreatic islet mass. The ICBC provides training in perfusion techniques, in basic principles of respiration and oxidative phosphorylation and measurement of oxygen consumption by different methods, and in all aspects of islet cell physiology and biochemistry. Aim 3: To pursue procedural and equipment advances: We will support the studies of collaborators at Penn and CHOP involving human islets affected by a range of pathophysiological conditions. We will also adapt our technology and expertise to the analysis of non-islet, metabolically relevant tissues, reflecting the complex, intercommunicating, multi-organ control required to maintain normal glucose homeostasis. Technological advances will include equipment upgrades and expansion of services to include measurement of mitochondrial membrane potential and perifusion of dispersed primary islet cells in a 6 well plate format. Aim 4: To embark on a new initiative for islet cell electrophysiology: Prompted by the research needs of DRC investigators, we established collaboration with our Physiology Department, widely acknowledged for excellence in cell membrane biophysics, to provide expert consultation and experimental services in this crucial aspect of pancreatic islet cell biology and disease. In sum, the Islet Cell Biology Core is well aligned with the overall goals of the DRC, enabling investigators to perform state of the art basic and clinical research. Correlation of our phenotypic analysis performed on genetically altered or metabolically challenged mice or human source material with in vivo metabolic phenotyping and high throughput sequencing performed by other DRC cores will deepen our insights with the potential for therapeutic translation.